RNA interfering (RNAi)-mediated gene silencing holds great promise for manipulating T cells to study basic T cell biology and for developing potential T cell targeted therapeutics.
Many autoimmune and/or inflammatory diseases are mediated by Th17 cells. These include rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and type 1 diabetes mellitus (Rao D D et al, Adv Drug Deliv Rev 61, 746-759 (2009); incorporated by reference herein.
The retinoic acid receptor related orphan receptor gamma 2 gene encodes RORγt. RORγt is required for the differentiation of Th17 cells. Th17 cells produce several inflammatory cytokines, including IL-17, IL-17F, IL-22 and IL-21 which all have been implicated in mediating the chronic inflammation that is characteristic of a number of autoimmune inflammatory diseases.
New therapeutics that specifically target Th17 cells rather than targeting members of the IL-17 family or ubiquitous IL-17 receptors are needed.